Effect of aflibercept on refractory macular edema associated with central retinal vein occlusion

Abstract

We would like to address several challenges arising from the article by Cohen et al.1Cohen M.N. Houston S.K. Juhn A. et al.Effect of aflibercept on refractory macular edema associated with central retinal vein occlusion.Can J Ophthalmol. 2016; 51: 342-347Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar that can be specifically summarized as follows:1.The comparative efficacy of the treatments with bevacizumab (Avastin; Genentech Inc, San Francisco, Calif.)/ranibizumab (Lucentis; Genentech Inc) and aflibercept (Eylea; Regeneron, Terrytown, N.Y.) could not be evaluated because the design of this study lacked a real washout period, which is essential between the 2 periods of treatment in terms of aliased effects. Thus, the impact of significant carryover effects may be confounded with direct treatment effects because these effects could not be estimated separately; carryover effects may bias the interpretation of data analysis.2.Despite significant improvements in visual acuity and central foveal thickness after aflibercept treatment, the final results of this study were unsatisfactory. The fact that 70.5% of patients had unresolved macular edema indicates that the disease process is still active and progressive, requiring further treatment with antiangiogenic agents. Most likely, there was a chronic retinal capillaropathy because of permanent breakdown of the inner and outer blood–retinal barriers, which was temporarily relieved by reduction of edematous component with treatment. However, the pathology was incurable because of irreversible ischemic changes to the macular ganglion cell complex, close to the foveola, with macular edema being a minor factor.3.The follow-up period of this series was too short (mean 5.2 months) to conclude that aflibercept may be a useful alternative therapeutic option in patients with central retinal vein occlusion (RVO)–related macular edema that is refractory to other antiangiogenic agents. Importantly, the final outcomes of the Galileo and Copernicus studies2Ogura Y. Roider J. Korobelnik J.F. et al.Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion:18-month results of the phase 3 Galileo study.Am J Ophthalmol. 2014; 158: 1032-1038Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 3Heier J.S. Clark W.L. Boyer D.S. et al.Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion; two-year results from the Copernicus study.Ophthalmology. 2014; 121: 1414-1420Abstract Full Text Full Text PDF PubMed Scopus (218) Google Scholar regarding aflibercept treatment (the 76- and 100-week results, respectively) indicated a decline in the visual and anatomic improvements from those gained at week 24.4.We published a prospective clinical study4Călugăru D. Călugăru M. Intravitreal bevacizumab in acute/central/hemicentral retinal vein occlusions: three-year results of a prospective clinical study.J Ocul Pharmacol Ther. 2015; 31: 78-86Crossref PubMed Scopus (58) Google Scholar on the 3-year results of bevacizumab treatment in patients with acute (≤1 month after the occlusion was diagnosed) central/hemicentral RVOs. This was the first study to report evidence suggesting that early treatment applied immediately after the clinical onset of venous occlusion provided significant and sustained improvements in visual acuity and central foveal thickness with inactive disease in most phakic patients with acute central/hemicentral RVOs, making this treatment option a rational and viable therapeutic strategy. Altogether, regardless of the antiangiogenic agents used (bevacizumab/ranibizumab/aflibercept), the efficacy of therapy depends primarily on the promptness of the therapy after RVO diagnosis.5Călugăru D. Călugăru M. Comment on: “Central retinal vein occlusion: modifying current treatment protocols.”.Eye. 2016; 30: 1395-1396Crossref PubMed Scopus (3) Google Scholar The authors have no proprietary or commercial interest in any materials discussed in this article. Re: Effect of Aflibercept on Refractory Macular Edema Associated with Central Retinal Vein OcclusionCanadian Journal of OphthalmologyVol. 52Issue 1PreviewAuthors’ Reply to Letter to the Editor (CJO_2016_683; Calugaru et al): Full-Text PDF